Mary Mohrin Pilot Scope (UK Cares) Hidden in Plain Sight: Developing a Radon Exposure Chamber to Unmask Environmental DNA Damage in the Blood & Immune Systems

This project will develop and validate a controlled radon exposure chamber to uncover how environmentally relevant radon doses drive DNA damage and functional decline in the blood and immune systems, with a particular focus on hematopoietic stem cell (HSC) aging and leukemogenic risk. Radon is a ubiquitous, invisible residential carcinogen in Kentucky, yet its direct effects on human stem and immune cells remain poorly characterized, leaving a critical gap in environmental health protection and cancer prevention. By engineering a chamber that delivers stable, quantifiable radon levels that mirror real-world home exposure, we will be able to systematically expose primary blood and immune cell samples and define dose–response relationships for genotoxic and functional injury. Using the chamber, we will characterize how radon induces DNA lesions, activates DNA damage response (DDR) pathways, and alters key features of HSC biology, including quiescence, self-renewal, and differentiation. Parallel analyses of immune cell subsets will assess how radon impairs immune competence and promotes chronic inflammatory signaling that can feed back on stem cell function. By integrating molecular readouts (e.g., DDR activation, mutational signatures) with functional assays (e.g., stem cell activity, clonogenic potential), the project will test the hypothesis that radon acts as a driver of stem cell aging and clonal hematopoiesis, thereby increasing leukemogenic risk even at exposure levels considered acceptable. The proposed work will generate a first-in-kind platform for radon exposure studies in blood and immune cells, create foundational mechanistic data on radon-induced stem cell and immune dysfunction, and provide high- impact preliminary evidence to support future NIH and environmental health grant applications. In the long term, these insights will inform radon risk assessment, guide biomarker development for exposed populations, and catalyze strategies to mitigate radon-related hematologic and immune disease in Kentucky and beyond.